Epigenetics

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We are interested in determining the epigenetic factors that regulate epidermal homeostasis and progression to neoplasia. The term epigenetics refers to the transmission of heritable information from parental to daughter cells distinct from the primary DNA sequence. The two major epigenetic mechanisms involve the covalent modification of either DNA itself or histones that wrap around the DNA. Modification of DNA occurs through the methylation of cytosine residues usually within CpG dinucleotides in mammalian cells and leads to gene repression. Histone proteins form octamers, composed of two copies of histone 2A, 2B, 3 and 4, around which 146bp of DNA loops to form the basic unit of chromatin known as a nucleosome. The histone tails that extrude from the nucleosome can be modified via methylation, acetylation, phosphorylation or ubiquitylation, which can lead to either transcriptional activation or repression. The different patterns of cytosine methylations and histone modifications contribute to the differences in gene expression patterns between different cell types.